Vascular Endothelial Growth Factor: Possible Role in Fetal Development and Placental Function

Abstract

Vascular endothelial growth factor (VEGF) is an endothelial cell mitogen with potent permeability properties. This growth factor exists in several isoforms; the most abundant form present in most tissues is VEGF₁₆₅. The different isoforms exhibit differences in biologic function. During development, VEGF is expressed in multiple embryonic and fetal tissues, with the highest levels found in the lung, kidney, and heart. Vascular endothelial growth factor is also expressed in placental tissues and fetal membranes, and this expression increases with advancing gestation. In the fetal heart and placenta, VEGF expression is inducible by hypoxia. Two receptors, KDR and Flt-1, have been identified for VEGF. They are widely expressed in vascular endothelial cells and are also found in placental tissues where VEGF is localized. In humans, Flt-1 appears to be the predominant receptor, whereas in the cow and sheep, KDR is the major receptor expressed. The presence of VEGF and its receptors in placental tissues throughout gestation strongly suggests that VEGF plays an important role in the development and maintenance of placental vascular function during pregnancy. The localization of VEGF in fetal membranes and the fetal surface of the placenta raises the possibility that VEGF may be involved in the regulation of amniotic fluid volume and composition.